RSV-specific antibodies and functional parts thereof

ABSTRACT

This application provides antibodies and functional equivalents thereof which are capable of specifically binding RSV, as well as means and methods for producing them.

CONTINUING APPLICATION DATA

This application is a continuation of U.S. patent application Ser. No.15/111,610, filed 14 Jul. 2016, which is the § 371 U.S. National Stageof International Application No. PCT/US2015/011391, filed 14 Jan. 2015,which claims the benefit of U.S. Provisional Application Ser. No.61/927,819, filed Jan. 15, 2014, each of which is incorporated byreference herein.

SEQUENCE LISTING

This application contains a Sequence Listing electronically submittedvia EFS-Web to the United States Patent and Trademark Office as an ASCIItext file entitled “RSVNG-103US2_ST25.txt” having a size of 20 kilobytesand created on Mar. 17, 2020. The information contained in the SequenceListing is incorporated by reference herein.

DESCRIPTION Field

This application relates to the field of biotechnology and medicine.

Background

Respiratory Syncytial Virus (RSV) is a common cold virus belonging tothe family of paramyxovirus. RSV is virulent, easily transmissible andthe most common cause of lower respiratory tract disease in children ofless than 2 years of age. Up to 98% of children attending day care willbe infected in a single RSV season. Between 0.5% and 3.2% of childrenwith RSV infection require hospitalization. Approximately 90,000hospital admissions and 4,500 deaths per year were reported in UnitedStates. Major risk factors for hospitalization due to RSV are prematurebirth, chronic lung disease, congenital heart disease, compromisedimmunity, and age younger than 6 weeks in otherwise healthy children.There is a need for additional treatment for RSV positive bronchiolitisbeside supportive care in the form of adequate nutrition and oxygentherapy. Antiviral therapies such as Ribavirin have not been proven tobe effective in RSV infection. One monoclonal antibody, Palivizumab(also called Synagis®), is registered for prophylaxis against RSVinfection. Palivizumab is a genetically engineered (humanized)monoclonal antibody to the fusion protein of RSV. While Palivizumab hasbeen a very effective prophylactic, alternative antibodies and therapiesproviding additional coverage against RSV would be advantageous.

It is an object to provide means and methods for counteracting and/orpreventing an RSV infection. It is a further object to providealternative and/or improved antibodies against RSV, or functionalequivalents of such antibodies, and to provide stable cells capable ofproducing antibodies or functional equivalents thereof against RSV.

SUMMARY

In accordance with the description, a synthetic, recombinant, orisolated antibody or a functional part thereof capable of specificallybinding Respiratory Syncytial Virus comprises:

-   -   a. a heavy chain variable region CDR1 sequence comprising a        sequence which is at least 70% identical to the sequence NYIIN        (SEQ ID NO: 1) or DYIIN (SEQ ID NO: 9), and    -   b. a heavy chain variable region CDR2 sequence comprising a        sequence which is at least 75% identical to the sequence        GIIPVLGTVHYAPKFQG (SEQ ID NO: 2) or GIIPVLGTVHYGPKFQG (SEQ ID        NO: 10), and    -   c. a heavy chain variable region CDR3 sequence comprising a        sequence which is at least 70% identical to the sequence        ETALVVSTTYLPHYFDN (SEQ ID NO: 3) or ETALVVSTTYRPHYFDN (SEQ ID        NO: 11), and    -   d. a light chain variable region CDR1 sequence comprising a        sequence which is at least 85% identical to the sequence        QASQDIVNYLN (SEQ ID NO: 4), and    -   e. a light chain variable region CDR2 sequence comprising a        sequence which is at least 70% identical to the sequence VASNLET        (SEQ ID NO: 5), and    -   f. a light chain variable region CDR3 sequence comprising a        sequence which is at least 70% identical to the sequence QQYDNLP        (SEQ ID NO: 6).        and wherein at least one amino acid in the heavy chain differs        from SEQ ID NO: 7 and said at least one amino acid is chosen        from:

Position relative to SEQ ID NO: 1 Amino Acid 19 K 23 K 28 T or L 29 F 30S or E 37 V 45 L 77 S 81 M 82 E or H 84 S 98 R

In another embodiment, the antibody or functional part comprises:

-   -   a. heavy chain variable region CDR1 sequence comprises a        sequence which differs by one amino acid from NYIIN (SEQ ID        NO: 1) or DYIIN (SEQ ID NO: 9),    -   b. heavy chain variable region CDR2 sequence comprises a        sequence which differs by one or two amino acids from        GIIPVLGTVHYAPKFQG (SEQ ID NO: 2) or GIIPVLGTVHYGPKFQG (SEQ ID        NO: 10),    -   c. heavy chain variable region CDR3 sequence comprises a        sequence which differs by one or two amino acid from        ETALVVSTTYLPHYFDN (SEQ ID NO: 3) or ETALVVSTTYRPHYFDN (SEQ ID        NO: 11),    -   d. light chain variable region CDR1 sequence comprises a        sequence which differs by one amino acid from QASQDIVNYLN (SEQ        ID NO: 4),    -   e. light chain variable region CDR2 sequence comprises a        sequence which differs by one amino acid from VASNLET (SEQ ID        NO: 5), and/or    -   f. light chain variable region CDR3 sequence comprises a        sequence which differs by one amino acid from QQYDNLP (SEQ ID        NO: 6).

In another embodiment, the antibody or functional part comprises

-   -   a. heavy chain variable region CDR1 sequence comprises NYIIN        (SEQ ID NO: 1) or DYIIN (SEQ ID NO: 9),    -   b. heavy chain variable region CDR2 sequence comprises        GIIPVLGTVHYAPKFQG (SEQ ID NO: 2) or GIIPVLGTVHYGPKFQG (SEQ ID        NO: 10),    -   c. heavy chain variable region CDR3 sequence comprises        ETALVVSTTYLPHYFDN (SEQ ID NO: 3) or ETALVVSTTYRPHYFDN (SEQ ID        NO: 11),    -   d. light chain variable region CDR1 sequence comprises        QASQDIVNYLN (SEQ ID NO: 4),    -   e. light chain variable region CDR2 sequence comprises VASNLET        (SEQ ID NO: 5), and    -   f. light chain variable region CDR3 sequence comprises QQYDNLP        (SEQ ID NO: 6).

In a further embodiment, the antibody or functional part comprises atleast the following amino acids in the heavy chain variable region thatdiffer from SEQ ID NO: 7:

Position relative to SEQ ID NO: 7 Amino Acid 28 L 30 E 31 D 37 V 61 G 81M 82 E 84 S

In an additional embodiment, at least the following amino acids in theheavy chain variable region that differ from SEQ ID NO: 7:

Position relative to SEQ ID NO: 7 Amino Acid 37 V 81 M 82 E 84 S

In a further embodiment, the antibody or functional part comprises atleast the following amino acids in the heavy chain variable region thatdiffer from SEQ ID NO: 7:

Position relative to SEQ ID NO: 7 Amino Acid 37 V 45 L 81 M 82 E 84 S

In an additional embodiment, the antibody or functional part comprisesat least the following amino acids in the heavy chain variable regionthat differ from SEQ ID NO: 7:

Position relative to SEQ ID NO: 7 Amino Acid 19 K 23 K 28 T 29 F 30 S 37V 45 L 81 M 82 E 84 S

In a further embodiment, the antibody or functional part comprises atleast the following amino acids in the heavy chain variable region thatdiffer from SEQ ID NO: 7:

Position relative to SEQ ID NO: 7 Amino Acid 30 E 31 D 37 V 61 G 81 M 82E 84 S

In an additional embodiment, the antibody or functional part comprisesthe following amino acids in the heavy chain variable region that differfrom SEQ ID NO: 7:

Position relative to SEQ ID NO: 7 Amino Acid 30 E 31 D 37 V 61 G 81 M 82E 84 S 109 R

In an additional embodiment, the antibody or functional part comprisesat least the following amino acids in the heavy chain variable regionthat differ from SEQ ID NO: 7:

Position relative to SEQ ID NO: 7 Amino Acid 19 K 23 K 28 L 30 E 31 D 37V 61 G 77 S 81 M 84 S 98 R

In an additional embodiment, the antibody or functional part comprisesat least the following amino acids in the heavy chain variable regionthat differ from SEQ ID NO: 7:

Position relative to SEQ ID NO: 7 Amino Acid 19 K 23 K 28 L 30 E 31 D 37V 61 G 81 M 84 S

In a further embodiment, the antibody or functional part comprises atleast the following amino acids in the heavy chain variable region thatdiffer from SEQ ID NO: 7:

Position relative to SEQ ID NO: 7 Amino Acid 19 K 23 K 28 L 30 E 31 D 37V 61 G 77 S 81 M 82 E 84 S

In an additional embodiment, the antibody or functional part comprisesat least the following amino acids in the heavy chain variable regionthat differ from SEQ ID NO: 7:

Position relative to SEQ ID NO: 7 Amino Acid 19 K 23 K 28 L 30 E 31 D 37V 61 G 77 S 81 M 84 S

In a further embodiment, the heavy chain variable region CDR1 sequencecomprises a sequence which differs by one amino acid from either NYIIN(SEQ ID NO: 1) or DYIIN (SEQ ID NO: 9), the heavy chain variable regionCDR2 sequence comprises a sequence which differs by one or two aminoacids from GIIPVLGTVHYAPKFQG (SEQ ID NO: 2) or GIIPVLGTVHYGPKFQG (SEQ IDNO: 10), and/or the heavy chain variable region CDR3 sequence comprisinga sequence which differs by one or two amino acids fromETALVVSTTYLPHYFDN (SEQ ID NO: 3) or ETALVVSTTYRPHYFDN (SEQ ID NO: 11).

In a further embodiment, the light chain variable region CDR1 sequencecomprising a sequence which differs by one amino acid from QASQDIVNYLN(SEQ ID NO: 4), the light chain variable region CDR2 sequence comprisinga sequence which differs by one amino acid from VASNLET (SEQ ID NO: 5),and/or the light chain variable region CDR3 comprises a sequence whichdiffers by one amino acid from QQYDNLP (SEQ ID NO: 6).

In a further embodiment, the heavy chain variable region CDR1 sequencecomprises NYIIN (SEQ ID NO: 1) or DYIIN (SEQ ID NO: 9), the heavy chainvariable region CDR2 sequence comprises GIIPVLGTVHYAPKFQG (SEQ ID NO: 2)or GIIPVLGTVHYGPKFQG (SEQ ID NO: 10), and/or the heavy chain variableregion CDR3 sequence comprises ETALVVSTTYLPHYFDN (SEQ ID NO: 3) orETALVVSTTYRPHYFDN (SEQ ID NO: 11).

In an additional embodiment, the light chain variable region CDR1sequence comprises QASQDIVNYLN (SEQ ID NO: 4), the light chain variableregion CDR2 sequence comprises VASNLET (SEQ ID NO: 5), and/or the lightchain variable region CDR3 comprises QQYDNLP (SEQ ID NO: 6).

In one embodiment, a synthetic, recombinant, or isolated antibody orfunctional part thereof capable of specifically binding to a RSV Fantigen comprises

-   -   a. a heavy chain variable region CDR1 sequence comprising the        amino acid sequence DYIIN (SEQ ID NO: 9), and    -   b. a heavy chain variable region CDR2 sequence comprising the        amino acid sequence GIIPVLGTVHYGPKFQG (SEQ ID NO: 10), and    -   c. a heavy chain variable region CDR3 sequence comprising the        amino acid sequence ETALVVSTTYRPHYFDN (SEQ ID NO: 11), and    -   d. a light chain variable region CDR1 sequence comprising the        amino acid sequence QASQDIVNYLN (SEQ ID NO: 4), and    -   e. a light chain variable region CDR2 sequence comprising the        amino acid sequence VASNLET (SEQ ID NO: 5), and    -   f. a light chain variable region CDR3 comprising the amino acid        sequence QQYDNLP (SEQ ID NO: 6).

In another embodiment, a synthetic, recombinant, or isolated antibody ora functional part thereof capable of specifically binding to a RSV Fantigen comprises:

-   -   a. a heavy chain variable region CDR1 sequence comprising the        amino acid sequence DYIIN (SEQ ID NO: 9), and    -   b. a heavy chain variable region CDR2 sequence comprising the        amino acid sequence GIIPVLGTVHYGPKFQG (SEQ ID NO: 10), and    -   c. a heavy chain variable region CDR3 sequence comprising the        amino acid sequence ETALVVSTTYLPHYFDN (SEQ ID NO: 3), and    -   d. a light chain variable region CDR1 sequence comprising the        amino acid sequence QASQDIVNYLN (SEQ ID NO: 4), and    -   e. a light chain variable region CDR2 sequence comprising the        amino acid sequence VASNLET (SEQ ID NO: 5), and    -   f. a light chain variable region CDR3 comprising the amino acid        sequence QQYDNLP (SEQ ID NO: 6).

In a further embodiment, the antibody or functional part has an Fcregion having Y at position 252Y, T at position 254T, and E at position256, wherein the numbering corresponds to the EU index in Kabat.

In yet a further embodiment, a method of inhibiting RSV infection in asubject comprising administering the antibody or functional partdescribed herein to the subject.

In yet a further embodiment, a synthetic, recombinant, or isolatednucleic acid sequence encodes the antibody or functional part describedherein.

Additional objects and advantages will be set forth in part in thedescription which follows, and in part will be obvious from thedescription, or may be learned by practice. The objects and advantageswill be realized and attained by means of the elements and combinationsparticularly pointed out in the appended claims.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory onlyand are not restrictive of the claims.

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate one (several) embodiment(s) andtogether with the description, serve to explain the principles describedherein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and B are a representation of the sequence for the D25 heavychain and several heavy chain variants (J, L, and LA).

FIG. 2 is a representation of the sequence for the heavy chain ofseveral optimized variants (1G7, 1F5, 2D10).

FIGS. 3A and B are a representation of the sequence for the heavy chainof four additional variants of the optimized variant 1G7. The variants(1G7-GLM, B12-1, E3-5, and E9-2) were made to alter pI by incorporatinggermline residues.

FIGS. 4A and B show in vitro activity of D25 and several variants in amicroneutralization assay.

FIGS. 5A and B show that D25 and several variants offer protectionagainst RSV A2 and RSV B subtype challenge.

FIG. 6 shows the results of a cotton rat RSV A2 challenge in animalstreated with 1G7, 1F5, D25 (designated in the figure as D25 wt), or noantibody.

FIGS. 7A and B show that 1G7 protects against both RSV A2 and RSV B9320.Lung titers of RSV are plotted as a function of the serum concentrationof human IgG at the time of harvest.

FIGS. 8A and B show the neutralization of both RSV A2 and RSV B9320 byvarious antibodies.

FIGS. 9A and B show the epitope for binding of 1G7 as defined bymonoclonal antibody resistant mutants.

FIG. 10 shows the results of a neutralization assay against clinicalisolates of RSV.

DESCRIPTION OF THE SEQUENCES

Table 1 provides a listing of certain sequences referenced in presentembodiments.

TABLE 1 SEQ Description Sequence ID NO D25 HC CDR1 NYIIN  1 D25 HC CDR2GIIPVLGTVHYAPKFQG  2 D25 HC CDR3 ETALVVSTTYLPHYFDN  3 D25 LC CDR1QASQDIVNYLN  4 D25 LC CDR2 VASNLET  5 D25 LC CDR3 QQYDNLP  6 D25 heavy        10         20         30         40         50  7 chain variableQVQLVQSGAE VKKPGSSVMV SCQASGGPLR NYIINWLRQA PGQGPEWMGG region        60         70         80         90        100IIPVLGTVHY APKFQGRVTI TADESTDTAY IHLISLRSED TAMYYCATET       110        120    126 ALVVSTTYLP HYFDNWGQGT LVTVSS D25 lightDIQMTQSPSS LSAAVGDRVT ITCQASQDIV NYLNWYQQKP GKAPKLLIYV  8 chain variableASNLETGVPS RFSGSGSGTD FSLTISSLQP EDVATYYCQQ YDNLPLTFGG region GTKVEIKRTVAlternative DYIIN  9 HC CDR1 Alternative GIIPVLGTVHYGPKFQG 10 HC CDR2Alternative ETALVVSTTYRPHYFDN 11 HC CDR3 Alternative ETALVVSETYLPHYFDN22 HC CDR3 J variantQVQLVQSGAE VKKPGSSVMV SCQASGGPLR NYIINWVRQA PGQGPEWMGG 12 heavy chainIIPVLGTVHY APKFQGRVTI TADESTDTAY MELSSLRSED TAMYYCATET variableALVVSTTYLP HYFDNWGQGT LVTVSS region L variantQVQLVQSGAE VKKPGSSVMV SCQASGGPLR NYIINWVRQA PGQGLEWMGG 13 heavy chainIIPVLGTVHY APKFQGRVTI TADESTDTAY MELSSLRSED TAMYYCATET variableALVVSTTYLP HYFDNWGQGT LVTVSS region LA variantQVQLVQSGAE VKKPGSSVKV SCKASGGTFS NYIINWVRQA PGQGLEWMGG 14 heavy chainIIPVLGTVHY APKFQGRVTI TADESTDTAY MELSSLRSED TAMYYCATET variableALVVSTTYLP HYFDNWGQGT LVTVSS region Alternative QVQLVQSGAE VKKPGSSVMV SCQASGGLLE DYIINWVRQA PGQGPEWMGG 15 heavy chainIIPVLGTVHY GPKFQGRVTI TADESTDTAY MELSSLRSED TAMYYCATET variable regionALVVSTTYLP HYFDNWGQGT LVTVSS 1G7QVQLVQSGAE VKKPGSSVMV SCQASGGLLE DYIINWVRQA PGQGPEWMGG 23 heavy chainIIPVLGTVHY GPKFQGRVTI TADESTDTAY MELSSLRSED TAMYYCATET variable regionALVVSTTYLP HYFDNWGQGT LVTVSS 1F5QVQLVQSGAE VKKPGSSVMV SCQASGGPLE DYIINWVRQA PGQGPEWMGG 16 heavy chainIIPVLGTVHY GPKFQGRVTI TADESTDTAY MELSSLRSED TAMYYCATET variableALVVSTTYLP HYFDNWGQGT LVTVSS region 2D10QVQLVQSGAE VKKPGSSVMV SCQASGGPLE DYIINWVRQA PGQGPEWMGG 17 heavy chainIIPVLGTVHY GPKFQGRVTI TADESTDTAY MELSSLRSED TAMYYCATET variableALVVSTTYRP HYFDNWGQGT LVTVSS region 1G7-GLMQVQLVQSGAE VKKPGSSVKV SCKASGGLLE DYIINWVRQA PGQGPEWMGG 18 heavy chainIIPVLGTVHY GPKFQGRVTI TADESTSTAY MHLSSLRSED TAMYYCARET variableALVVSTTYLP HYFDNWGQGT LVTVSS region B12-1QVQLVQSGAE VKKPGSSVKV SCKASGGLLE DYIINWVRQA PGQGPEWMGG 19 heavy chainIIPVLGTVHY GPKFQGRVTI TADESTDTAY MHLSSLRSED TAMYYCATET variableALVVSTTYLP HYFDNWGQGT LVTVSS region E3-5QVQLVQSGAE VKKPGSSVKV SCKASGGLLE DYIINWVRQA PGQGPEWMGG 20 heavy chainIIPVLGTVHY GPKFQGRVTI TADESTSTAY MELSSLRSED TAMYYCATET variableALVVSTTYLP HYFDNWGQGT LVTVSS region E9-2QVQLVQSGAE VKKPGSSVKV SCKASGGLLE DYIINWVRQA PGQGPEWMGG 21 heavy chainIIPVLGTVHY GPKFQGRVTI TADESTSTAY MHLSSLRSED TAMYYCATET variableALVVSTTYLP HYFDNWGQGT LVTVSS region

DESCRIPTION OF THE EMBODIMENTS I. Antibodies or Functional Parts Thereof

Improved RSV-specific antibodies or functional parts thereof havingimproved properties as compared to other antibodies are provided. [0092]Antibodies or functional parts, e.g., antibodies or antigen-bindingfragments, variants, or derivatives thereof include, but are not limitedto, polyclonal, monoclonal, human, humanized, or chimeric antibodies,single chain antibodies, epitope-binding fragments, e.g., Fab, Fab′ andF(ab′)2, Fd, Fvs, single-chain Fvs (scFv), single-chain antibodies,disulfide-linked Fvs (sdFv), fragments comprising either a VL or VHdomain, fragments produced by a Fab expression library. ScFv moleculesare known in the art and are described, e.g., in U.S. Pat. No.5,892,019. Immunoglobulin or antibody molecules encompassed by thisdisclosure can be of any type (e.g., IgG, IgE, IgM, IgD, IgA, and IgY),class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2) or subclass ofimmunoglobulin molecule.

For example, the inventors have succeeded in generating RSV-specificantibodies with improved properties over prior RSV-specific antibodies,including improved protection against RSV A subtypes and RSV B subtypes,improved neutralization, and lower IC50 values. Such antibodies have aparticular high or strong affinity for RSV and are thereforeparticularly suitable for counteracting and/or at least in partpreventing an RSV infection and/or adverse effects of an RSV infection.Antibodies and functional parts thereof are synonymous with RSV-specificbinding molecules and include any full length antibodies or antibodyparts that are able to specifically bind RSV.

A. Antibodies or Functional Parts with Nongermline Residues Changed toGermline Residues

In one embodiment, at least one nongermline residue of the heavy chainvariable region of D25 (SEQ ID NO: 7) is changed to a germline residue.In another embodiment, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12nongermline residues of the heavy chain variable region of D25 residuesare switched back to a germline residue. In a further embodiment, atleast one nongermline residue may be changed to a germline residue andat least one CDR position may be modified relative to SEQ ID NO: 7.

One embodiment includes an isolated, synthetic, or recombinant antibodyor a functional part thereof capable of specifically binding RespiratorySyncytial Virus and comprising:

-   -   a) a heavy chain CDR1 sequence comprising a sequence which is at        least 70%, 75%, 80%, 85%, 90%, or 94% identical to the sequence        NYIIN (SEQ ID NO: 1) or DYIIN (SEQ ID NO: 9),    -   b) a heavy chain CDR2 sequence comprising a sequence which is at        least 70%, 75%, 80%, 85%, 90%, or 94% identical to the sequence        GIIPVLGTVHYAPKFQG (SEQ ID NO: 2) or GIIPVLGTVHYGPKFQG (SEQ ID        NO: 10),    -   c) a heavy chain CDR3 sequence comprising a sequence which is at        least 70%, 75%, 80%, 85%, 90%, or 94% identical to the sequence        ETALVVSTTYLPHYFDN (SEQ ID NO: 3) or ETALVVSTTYRPHYFDN (SEQ ID        NO: 11),    -   d) a light chain CDR1 sequence comprising a sequence which is at        least 70%, 75%, 80%, 85%, 90%, or 94% identical to the sequence        QASQDIVNYLN (SEQ ID NO: 4),    -   e) a light chain CDR2 sequence comprising a sequence which is at        least 70%, 75%, 80%, 85%, 90%, or 94% identical to the sequence        VASNLET (SEQ ID NO: 5), and    -   f) a light chain CDR3 sequence comprising a sequence which is at        least 70%, 75%, 80%, 85%, 90%, or 94% identical to the sequence        QQYDNLP (SEQ ID NO: 6).        and wherein at least one amino acid in the heavy chain differs        from SEQ ID NO: 7 and said at least one amino acid is chosen        from:

TABLE 2 Position relative to SEQ ID NO: 7 Type of Change Amino Acid 19nongermline framework K changed to germline 23 nongermline framework Kchanged to germline 28 nongermline framework T or L changed to germline29 nongermline framework F changed to germline 30 nongermline frameworkS or E changed to germline 37 nongermline framework V changed togermline 45 nongermline framework L changed to germline 77 nongermlineframework S changed to germline 81 nongermline framework M changed togermline 82 nongermline framework E or H changed to germline 84nongermline framework S changed to germline 98 nongermline framework Rchanged to germline

“At least one amino acid in the heavy chain variable region differs fromSEQ ID NO: 7” means that the antibody or functional part must compriseat least one amino acid difference from SEQ ID NO: 7, although, in someembodiments, it may comprise more than one difference from SEQ ID NO: 7.In some embodiments it includes substitutions outlined in Table 2,deletions or alternative amino acids at positions listed in Table 2, ordifferences (including deletions, substitutions, or additions) inpositions not listed in Table 2. Position numbers in Table 2 areprovided relative to SEQ ID NO: 7 and the position number may notultimately be the same as the position number based on the consecutivenumbering of amino acids in the antibody or functional part of interest.Instead, position numbers are assigned based on alignment with SEQ IDNO: 7.

In one embodiment, the antibody or functional part includes a heavychain and/or a light chain, wherein the heavy chain variable region isat least 90% identical to SEQ ID NO: 7 or SEQ ID NO: 15 and wherein thelight chain variable region is at least 90% identical to SEQ ID NO: 8.In another embodiment, the heavy chain variable region is at least 91%,92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 7 orSEQ ID NO: 15. In another embodiment, the light chain variable region isat least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQID NO: 8.

In one embodiment, the antibody or functional part comprises a heavychain variable region CDR1 sequence comprises a sequence which differsby one amino acid from either NYIIN (SEQ ID NO: 1) or DYIIN (SEQ ID NO:9).

In one embodiment, the antibody or functional part comprises a heavychain variable region CDR2 sequence comprises a sequence which differsby one or two amino acids from GIIPVLGTVHYAPKFQG (SEQ ID NO: 2) orGIIPVLGTVHYGPKFQG (SEQ ID NO: 10).

In one embodiment, the antibody or functional part comprises a heavychain variable region CDR3 sequence comprising a sequence which differsby one or two amino acids from ETALVVSTTYLPHYFDN (SEQ ID NO: 3) orETALVVSTTYRPHYFDN (SEQ ID NO: 11).

In one embodiment, the antibody or functional part comprises a lightchain variable region CDR1 sequence comprising a sequence which differsby one amino acid from QASQDIVNYLN (SEQ ID NO: 4).

In one embodiment, the antibody or functional part comprises a lightchain variable region CDR2 sequence comprising a sequence which differsby one amino acid from VASNLET (SEQ ID NO: 5).

In one embodiment, the antibody or functional part comprises a lightchain variable region CDR3 comprises a sequence which differs by oneamino acid from QQYDNLP (SEQ ID NO: 6).

In a further embodiment, the antibody or functional part comprises aheavy chain variable region CDR1 sequence comprising a sequence whichdiffers by one amino acid from NYIIN (SEQ ID NO: 1) or DYIIN (SEQ ID NO:9), a heavy chain variable region CDR2 sequence comprising a sequencewhich differs by one or two amino acids from GIIPVLGTVHYAPKFQG (SEQ IDNO: 2) or GIIPVLGTVHYGPKFQG (SEQ ID NO: 10), a heavy chain variableregion CDR3 sequence comprising a sequence which differs by one or twoamino acid from ETALVVSTTYLPHYFDN (SEQ ID NO: 3) or ETALVVSTTYRPHYFDN(SEQ ID NO: 11), a light chain variable region CDR1 sequence comprisinga sequence which differs by one amino acid from QASQDIVNYLN (SEQ ID NO:4), a light chain variable region CDR2 sequence comprising a sequencewhich differs by one amino acid from VASNLET (SEQ ID NO: 5), and/or alight chain variable region CDR3 sequence comprising a sequence whichdiffers by one amino acid from QQYDNLP (SEQ ID NO: 6).

In some embodiments, the antibody or functional part comprises at leastone or up to all of the identical CDRs as SEQ ID NO: 7 (heavy chain)and/or SEQ ID NO: 8 (light chain).

In one embodiment, the antibody or functional part comprises a heavychain variable region CDR1 sequence comprising NYIIN (SEQ ID NO: 1) orDYIIN (SEQ ID NO: 9).

In one embodiment, the antibody or functional part comprises a heavychain variable region CDR2 sequence comprising GIIPVLGTVHYAPKFQG (SEQ IDNO: 2) or GIIPVLGTVHYGPKFQG (SEQ ID NO: 10).

In one embodiment, the antibody or functional part comprises a heavychain variable region CDR3 sequence comprising ETALVVSTTYLPHYFDN (SEQ IDNO: 3) or ETALVVSTTYRPHYFDN (SEQ ID NO: 11).

In one embodiment, the antibody of functional part comprises a heavychain variable region CDR1 sequence comprising NYIIN (SEQ ID NO: 1) orDYIIN (SEQ ID NO: 9), a heavy chain variable region CDR2 sequencecomprising GIIPVLGTVHYAPKFQG (SEQ ID NO: 2) or GIIPVLGTVHYGPKFQG (SEQ IDNO: 10), and/or a heavy chain variable region CDR3 sequence comprisingETALVVSTTYLPHYFDN (SEQ ID NO: 3) or ETALVVSTTYRPHYFDN (SEQ ID NO: 11).

In one embodiment, the antibody or functional part comprises a lightchain variable region CDR1 sequence comprises QASQDIVNYLN (SEQ ID NO:4).

In one embodiment, the antibody or functional part comprises a lightchain variable region CDR2 sequence comprises VASNLET (SEQ ID NO: 5).

In one embodiment, the antibody or functional part comprises a lightchain variable region CDR3 comprises QQYDNLP (SEQ ID NO: 6).

In one embodiment, the antibody of functional part comprises a lightchain variable region CDR1 sequence comprises QASQDIVNYLN (SEQ ID NO:4), a light chain variable region CDR2 sequence comprises VASNLET (SEQID NO: 5), and/or a light chain variable region CDR3 comprises QQYDNLP(SEQ ID NO: 6).

In a further embodiment, the antibody or functional part comprises aheavy chain variable region CDR1 sequence comprising NYIIN (SEQ IDNO: 1) or DYIIN (SEQ ID NO: 9), a heavy chain variable region CDR2sequence comprising GIIPVLGTVHYAPKFQG (SEQ ID NO: 2) orGIIPVLGTVHYGPKFQG (SEQ ID NO: 10), a heavy chain variable region CDR3sequence comprising ETALVVSTTYLPHYFDN (SEQ ID NO: 3) orETALVVSTTYRPHYFDN (SEQ ID NO: 11), a light chain variable region CDR1sequence comprising QASQDIVNYLN (SEQ ID NO: 4), a light chain variableregion CDR2 sequence comprising VASNLET (SEQ ID NO: 5), and/or a lightchain variable region CDR3 sequence comprising QQYDNLP (SEQ ID NO: 6).

In one embodiment, the antibody or functional part comprises a heavychain variable region comprising a sequence which is 95% identical inthe framework regions to a sequence chosen from SEQ ID NO: 12-21.

In one embodiment, the antibody or functional part comprises a heavychain variable region comprising a sequence which is identical in theframework regions to a sequence chosen from SEQ ID NO: 12-21.

In one embodiment, the antibody or functional part comprises at leastthe following amino acids in the heavy chain variable region that differfrom SEQ ID NO: 7:

TABLE 3 J Variant Position relative to SEQ ID NO: 7 Amino Acid 37 V 81 M82 E 84 SIn another embodiment, the differences provided in Table 3 are the onlydifferences from SEQ ID NO: 7. In one embodiment, the differencesprovided in Table 3 are not the only differences from SEQ ID NO: 7. Inanother embodiment, the light chain variable region comprises SEQ ID NO:8.

In one embodiment, the antibody or functional part comprises at leastthe following amino acids in the heavy chain variable region that differfrom SEQ ID NO: 7:

TABLE 4 L Variant Position relative to SEQ ID NO: 7 Amino Acid 37 V 45 L81 M 82 E 84 SIn another embodiment, the differences provided in Table 4 are the onlydifferences from SEQ ID NO: 7. In one embodiment, the differencesprovided in Table 4 are not the only differences from SEQ ID NO: 7. Inanother embodiment, the light chain variable region comprises SEQ ID NO:8.

In one embodiment, the antibody or functional part comprises at leastthe following amino acids in the heavy chain variable region that differfrom SEQ ID NO: 7:

TABLE 5 LA Variant Position relative to SEQ ID NO: 7 Amino Acid 19 K 23K 28 T 29 F 30 S 37 V 45 L 81 M 82 E 84 SIn another embodiment, the differences provided in Table 5 are the onlydifferences from SEQ ID NO: 7. In one embodiment, the differencesprovided in Table 5 are not the only differences from SEQ ID NO: 7. Inanother embodiment, the light chain variable region comprises SEQ ID NO:8.

In one embodiment, the antibody or functional part comprises at leastthe following amino acids in the heavy chain variable region that differfrom SEO ID NO: 7:

TABLE 6 IG7 Position relative to SEQ ID NO: 7 Amino Acid 28 L 30 E 31 D37 V 61 G 81 M 82 E 84 SIn another embodiment, the differences provided in Table 6 are the onlydifferences from SEQ ID NO: 7. In one embodiment, the differencesprovided in Table 6 are not the only differences from SEQ ID NO: 7. Inanother embodiment, the light chain variable region comprises SEQ ID NO:8.

In one embodiment, the antibody or functional part comprises at leastthe following amino acids in the heavy chain variable region that differfrom SEQ ID NO: 7:

TABLE 7 1F5 Position relative to SEQ ID NO: 7 Amino Acid 30 E 31 D 37 V61 G 81 M 82 E 84 SIn another embodiment, the differences provided in Table 7 are the onlydifferences from SEQ ID NO: 7. In one embodiment, the differencesprovided in Table 7 are not the only differences from SEQ ID NO: 7. Inanother embodiment, the light chain variable region comprises SEQ ID NO:8.

In one embodiment, the antibody or functional part comprises at leastthe following amino acids in the heavy chain variable region that differfrom SEQ ID NO: 7:

TABLE 8 2D10 Position relative to SEQ ID NO: 7 Amino Acid 30 E 31 D 37 V61 G 81 M 82 E 84 S 109 RIn another embodiment, the differences provided in Table 8 are the onlydifferences from SEQ ID NO: 7. In one embodiment, the differencesprovided in Table 8 are not the only differences from SEQ ID NO: 7. Inanother embodiment, the light chain variable region comprises SEQ ID NO:8.

In one embodiment, the antibody or functional part comprises at leastthe following amino acids in the heavy chain variable region that differfrom SEQ ID NO: 7.

TABLE 9 1G7-GLM Position relative to SEQ ID NO: 7 Amino Acid 19 K 23 K28 L 30 E 31 D 37 V 61 G 77 S 81 M 84 S 98 RIn another embodiment, the differences provided in Table 9 are the onlydifferences from SEQ ID NO: 7. In one embodiment, the differencesprovided in Table 9 are not the only differences from SEQ ID NO: 7. Inanother embodiment, the light chain variable region comprises SEQ ID NO:8.

In one embodiment, the antibody or functional part comprises at leastthe following amino acids in the heavy chain variable region that differfrom SEQ ID NO: 7:

TABLE 10 B12-1 Position relative to SEQ ID NO: 7 Amino Acid 19 K 23 K 28L 30 E 31 D 37 V 61 G 81 M 84 SIn another embodiment, the differences provided in Table 10 are the onlydifferences from SEQ ID NO: 7. In one embodiment, the differencesprovided in Table 10 are not the only differences from SEQ ID NO: 7. Inanother embodiment, the light chain variable region comprises SEQ ID NO:8.

In one embodiment, the antibody or functional part comprises at leastthe following amino acids in the heavy chain variable region that differfrom SEQ ID NO: 7:

TABLE 11 E3-5 Position relative to SEQ ID NO: 7 Amino Acid 19 K 23 K 28L 30 E 31 D 37 V 61 G 77 S 81 M 82 E 84 SIn another embodiment, the differences provided in Table 11 are the onlydifferences from SEQ ID NO: 7. In one embodiment, the differencesprovided in Table 11 are not the only differences from SEQ ID NO: 7. Inanother embodiment, the light chain variable region comprises SEQ ID NO:8.

In one embodiment, the antibody or functional part comprises at leastthe following amino acids in the heavy chain variable region that differfrom SEQ ID NO: 7:

TABLE 12 E9-2 Position relative to SEQ ID NO: 7 Amino Acid 19 K 23 K 28L 30 E 31 D 37 V 61 G 77 S 81 M 84 SIn another embodiment, the differences provided in Table 12 are the onlydifferences from SEQ ID NO: 7. In one embodiment, the differencesprovided in Table 12 are not the only differences from SEQ ID NO: 7. Inanother embodiment, the light chain variable region comprises SEQ ID NO:8.

In one embodiment, the antibody or functional part comprises a heavychain variable region sequence comprising a sequence which is at least70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to thesequence of SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15,SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, or SEQ ID NO: 21. In another embodiment, the antibody or functionalpart comprises a heavy chain sequence variable region comprising asequence which is at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%,or 100% identical to the framework (i.e., non CDR) sequence of SEQ IDNO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, or SEQ ID NO:21.

In another embodiment, the antibody or functional part comprises a lightchain variable region sequence comprising a sequence which is at least70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to thesequence DIQMTQSPSSLSAAVGDRVTIT CQASQDIVNYLNWYQQKPGKAPKLLIYVASNLETGVPSRFSGSGSGTDF SLTISSLQPED VATYYCQQYDNLPLTFGGGTKVEIKRTV (SEQ ID NO: 8).

In other embodiments, conservative amino acid substitution is applied.Conservative amino acid substitution involves substitution of one aminoacid with another with generally similar properties (size,hydrophobicity, etc.) such that the overall functioning is likely not tobe seriously affected.

B. Antibodies or Functional Parts with Improved CDRs

In one embodiment, the antibody or functional part may comprise at leastone CDR mutation relative to the CDRs present in SEQ ID NO: 7. In oneembodiment, the antibody or functional part may comprise at least one ofthe changes in Table 13. In another embodiment, the antibody orfunctional part may comprise one, two, or all three of the changes inTable 13.

TABLE 13 Position relative to SEQ ID NO: 7 Type of Change Amino Acid 31CDR modification D 61 CDR modification G 109 CDR modification R

Another embodiment includes an isolated, synthetic, or recombinantantibody or a functional part thereof capable of specifically binding toa RSV F antigen and comprising a heavy chain variable region CDR1sequence comprising the amino acid sequence DYIIN (SEQ ID NO: 9), aheavy chain variable region CDR2 sequence comprising the amino acidsequence GIIPVLGTVHYAPKFQG (SEQ ID NO: 2), a heavy chain variable regionCDR3 sequence comprising the amino acid sequence ETALVVSTTYLPHYFDN (SEQID NO: 3), a light chain variable region CDR1 sequence comprising theamino acid sequence QASQDIVNYLN (SEQ ID NO: 4), a light chain variableregion CDR2 sequence comprising the amino acid sequence VASNLET (SEQ IDNO: 5), and a light chain variable region CDR3 comprising the amino acidsequence QQYDNLP (SEQ ID NO: 6).

Another embodiment includes an isolated, synthetic, or recombinantantibody or a functional part thereof capable of specifically binding toa RSV F antigen and comprising a heavy chain variable region CDR1sequence comprising the amino acid sequence NYIIN (SEQ ID NO: 1), aheavy chain variable region CDR2 sequence comprising the amino acidsequence GIIPVLGTVHYGPKFQG (SEQ ID NO: 10), a heavy chain variableregion CDR3 sequence comprising the amino acid sequenceETALVVSTTYLPHYFDN (SEQ ID NO: 3), a light chain variable region CDR1sequence comprising the amino acid sequence QASQDIVNYLN (SEQ ID NO: 4),a light chain variable region CDR2 sequence comprising the amino acidsequence VASNLET (SEQ ID NO: 5), and a light chain variable region CDR3comprising the amino acid sequence QQYDNLP (SEQ ID NO: 6).

Another embodiment includes an isolated, synthetic, or recombinantantibody or a functional part thereof capable of specifically binding toa RSV F antigen and comprising a heavy chain variable region CDR1sequence comprising the amino acid sequence NYIIN (SEQ ID NO: 1), aheavy chain variable region CDR2 sequence comprising the amino acidsequence GIIPVLGTVHYAPKFQG (SEQ ID NO: 2), a heavy chain variable regionCDR3 sequence comprising the amino acid sequence ETALVVSTTYRPHYFDN (SEQID NO: 11), a light chain variable region CDR1 sequence comprising theamino acid sequence QASQDIVNYLN (SEQ ID NO: 4), a light chain variableregion CDR2 sequence comprising the amino acid sequence VASNLET (SEQ IDNO: 5), and a light chain variable region CDR3 comprising the amino acidsequence QQYDNLP (SEQ ID NO: 6).

In another embodiment, an isolated, synthetic, or recombinant antibodyor functional part thereof comprises a heavy chain variable regioncomprising heavy chain CDR1, CDR2, and CDR3 and a light chain comprisinglight chain CDR1, CDR2, and CDR3, wherein at least one, two, or allthree of the heavy chain CDRs are chosen from column A, the remainingheavy chain CDRs (if any) are chosen from column B, and the light chainCDRs comprise column C in Table 14. Thus, in one embodiment, the lightchain CDRs are provided in Table 14 column C and the heavy chain CDRsmay be mixed-and-matched from columns A and B so long as the heavy chainhas one of each of CDR1, CDR2, and CDR3.

TABLE 14 Alternative CDRs of One Set of Embodiments A B CAlternative CDRs D25 CDRs Light Chain CDRs CDR1 DYIIN NYIIN QASQDIVNYLNSEQ ID NO: 9) (SEQ ID NO: 1) (SEQ ID NO: 4) CDR2 GIIPVLGTVHYGPKFQGGIIPVLGTVHYAPKFQG VASNLET (SEQ ID NO: 10) (SEQ ID NO: 2),(SEQ ID NO: 5), CDR3 ETALVVSTTYRPHYFDN ETALVVSTTYLPHYFDN QQYDNLP(SEQ ID NO: 11) (SEQ ID NO: 3), (SEQ ID NO: 6).

The various alternative CDR embodiments do not necessarily contain anyof the nongermline to germline mutations discussed above in section I.A,but any or all of those may optionally be present.

In one embodiment, the antibody or functional part may comprise at leastone of the alternative heavy chain CDRs from Table 14 and may have atleast one other CDR modification. Specifically, in yet anotherembodiment, the antibody or functional part may comprise a heavy chainCDR1 sequence comprising a sequence which differs by one amino acid fromNYIIN (SEQ ID NO: 1), a heavy chain CDR2 sequence comprises a sequencewhich differs by one or two amino acids from GIIPVLGTVHYAPKFQG (SEQ IDNO: 2), a heavy chain CDR3 sequence comprises a sequence which differsby one or two amino acid from ETALVVSTTYLPHYFDN (SEQ ID NO: 3), a lightchain CDR1 sequence comprises a sequence which differs by one amino acidfrom QASQDIVNYLN (SEQ ID NO: 4), a light chain CDR2 sequence comprises asequence which differs by one amino acid from VASNLET (SEQ ID NO: 5),and/or a light chain CDR3 sequence comprises a sequence which differs byone amino acid from QQYDNLP (SEQ ID NO: 6), wherein at least one ofheavy chain CDR1 is DYIIN SEQ ID NO: 9), heavy chain CDR2 isGIIPVLGTVHYGPKFQG (SEQ ID NO: 10), or heavy chain CDR3 isETALVVSTTYRPHYFDN (SEQ ID NO: 11).

C. Antibodies or Functional Parts with Improved Half-Life

In one embodiment, additional modifications may be made to antibodies orfunctional parts described herein to improve their half-life. In oneembodiment, mutations such as deletion, addition, or substitutionmutations may be made to the antibodies or functional parts to improvetheir half-life. In one embodiment, the Fc region may be mutated toinclude one, two, or all three of the following substitutions M252Y,S254T, and T256E, wherein the numbering corresponds to the EU index inKabat. In one embodiment, the Fc region may be mutated to include all ofthe following substitutions M252Y, S254T, and T256E, wherein thenumbering corresponds to the EU index in Kabat. Dall'Acqua et al.,Properties of Human IgG1s Engineered for Enhanced Binding to theNeonatal Fc Receptor (FcRn), J Biol Chem 281(33):23514-23524 (2006). Theembodiment with all three substitutions is denoted as the YTE variant.Expressed differently, in one embodiment, the antibody or functionalpart has an Fc region having Y at position 252Y, T at position 254T, andE at position 256, wherein the numbering corresponds to the EU index inKabat.

D. Other Characteristics of Antibodies and Functional Parts Thereof

In certain embodiment, the antibody or functional part has an IC50 valueof less than 10 ng/ml in an in vitro neutralization assay wherein HEp-2cells are infected with RSV and the antibody or functional part. Inanother embodiment, the IC50 is 9 ng/ml, 8 ng/ml, 7 ng/ml, 6 ng/ml, 5ng/ml, 4 ng/ml, 3 ng/ml, or 2 ng/ml or less for RSV subtype A and/or RSVsubtype B. In one embodiment, the IC50 is measured in the in vitroneutralization assay described in the examples, optionally for RSV A2and/or RSV B9320.

In one embodiment, the antibodies and functional parts thereof areeffective at neutralizing RSV subtype A strains. In one embodiment, theantibodies and functional parts thereof are effective at neutralizingRSV subtype B strains. In another embodiment, the antibodies andfunctional parts thereof are effective at neutralizing both RSV subtypeA and B strains.

As used herein, the term antibody or functional part thereof is used inthe broadest sense. It may be man-made such as monoclonal antibodies(mAbs) produced by conventional hybridoma technology, recombinanttechnology and/or a functional fragment thereof. It may include bothintact immunoglobulin molecules for example a polyclonal antibody, amonoclonal antibody (mAb), a monospecific antibody, a bispecificantibody, a polyspecific antibody, a human antibody, a humanizedantibody, an animal antibody (e.g. camelid antibody), chimericantibodies, as well as portions, fragments, regions, peptides andderivatives thereof (provided by any known technique, such as, but notlimited to, enzymatic cleavage, peptide synthesis, or recombinanttechniques), such as, for example, immunoglobulin devoid of lightchains, Fab, Fab′, F(ab′)₂, Fv, scFv, antibody fragment, diabody, Fd,CDR regions, or any portion or peptide sequence of the antibody that iscapable of binding antigen or epitope. In one embodiment, the functionalpart is a single chain antibody, a single chain variable fragment(scFv), a Fab fragment, or a F(ab′)₂ fragment.

An antibody or functional part is said to be “capable of binding” amolecule if it is capable of specifically reacting with the molecule tothereby bind the molecule to the antibody. Antibody fragments orportions may lack the Fc fragment of intact antibody, clear more rapidlyfrom the circulation, and may have less non-specific tissue binding thanan intact antibody. Examples of antibody may be produced from intactantibodies using methods well known in the art, for example byproteolytic cleavage with enzymes such as papain (to produce Fabfragments) or pepsin (to produce F(ab′)₂ fragments). Portions ofantibodies may be made by any of the above methods, or may be made byexpressing a portion of the recombinant molecule. For example, the CDRregion(s) of a recombinant antibody may be isolated and subcloned intoan appropriate expression vector.

In one embodiment, an antibody or functional part is a human antibody.The use of human antibodies for human therapy may diminish the chance ofside effects due to an immunological reaction in a human individualagainst nonhuman sequences. In another embodiment, the antibody orfunctional part is humanized. In another embodiment, an antibody orfunctional part is a chimeric antibody. This way, sequences of interest,such as for instance a binding site of interest, can be included into anantibody or functional part.

In one embodiment, the antibody may have an IgG, IgA, IgM, or IgEisotype. In one embodiment, the antibody is an IgG.

II. Nucleic Acids Encoding Antibodies and Functional Parts Thereof

The present embodiments further provides an isolated, synthetic, orrecombinant nucleic acid sequence encoding any of the antibodies orfunctional parts described in section LA or I.B above. Such nucleic acidis for instance isolated from a B-cell which is capable of producing anantibody or functional part. Such nucleic acids encode the heavy andlight chain sequences set forth herein. Alternatively, such nucleicacids encode heavy and light chain sequences comprising the heavy andlight chain CDRs, respectively, set forth herein. In some embodiments,the nucleic acids will encode functional parts of the antibodiesdescribed herein. Due to the degeneracy of the nucleic acid code,multiple nucleic acids will encode the same amino acid and all areencompassed herein.

III. Methods of Use

A. Methods of Use of Antibodies or Functional Parts

In one embodiment, an antibody or functional part may be used in amethod of treatment or as a medicine. The method may be used forcounteracting or at least in part preventing an RSV infection or forcounteracting or at least in part preventing adverse effects of an RSVinfection. The method also comprises administering to an individual inneed thereof a therapeutically effective amount of an antibody orfunctional part as described herein. In one embodiment, the individualin need thereof is a human patient.

In one embodiment, in order to counteract RSV, an antibody or functionalpart may be administered to an individual before an RSV infection hastaken place, in other words as a prophylactic agent. Alternatively, anantibody or functional part may be administered when an individual isalready infected by RSV. Said antibody or functional part may beadministered to individuals with an increased risk of RSV infection,such as for instance children with premature birth, individuals withchronic lung disease, congenital heart disease and/or compromisedimmunity, children with an age younger than 6 weeks. Children withpremature birth include both infants in their first year of life, aswell as children in their second year of life and older children whoremain at risk of RSV infection. Also elderly people have an increasedrisk of RSV infection and thus may be targeted for administration basedon risk. The antibodies or functional parts may also be administered toindividuals who have had a prior RSV infection.

For therapeutic application, antibodies or functional parts aretypically combined with a pharmaceutically acceptable carrier, adjuvant,diluent and/or excipient. In one embodiment, the antibodies orfunctional parts are combined with water for injection, In anotherembodiment, they are prepared in a sterile, preservative-free liquidsolution with histidine, glycine, and chloride. In another embodiment,examples of suitable carriers for instance comprise keyhole limpethaemocyanin (KLH), serum albumin (e.g. BSA or RSA) and ovalbumin. Inanother embodiment, said suitable carrier comprises a solution like forexample saline. In other embodiments, the antibodies or functional partsare provided in a lyophilized form and mixed with water for injectionprior to administration.

B. Methods of Use of Nucleic Acids Encoding Antibodies or FunctionalParts

In yet another embodiment a nucleic acid encoding an antibody orfunctional part may be administered. Upon administration of such nucleicacid, antibodies or functional parts are produced by the host'smachinery. Produced antibodies or functional parts are capable ofpreventing and/or counteracting RSV infection and/or the adverse effectsof an RSV infection.

A nucleic acid encoding a functional part of an antibody refers anucleic acid at least 30 base pairs long, at least 50 base pairs long,or at least 100 base pairs long, comprising at least one expressioncharacteristic (in kind not necessarily in amount) as a nucleic acidencoding an antibody. In one embodiment, a nucleic acid encoding afunctional part of an antibody at least encodes an amino acid sequencecomprising two or optionally three CDRs of the antibodies describedherein.

IV. Methods of Making Antibodies and Functional Parts

An isolated antibody producing cell capable of producing an antibody orfunctional part is also provided. The antibodies or functional partsdescribed herein may be manufactured from a hybridoma that secretes theantibody or from a recombinantly produced cell that has been transformedor transfected with a gene or genes encoding the antibody or functionalpart.

One embodiment includes a method of producing the antibody or functionalpart by culturing host cells under conditions wherein a nucleic acid isexpressed to produce the antibody, followed by recovering the antibody.A variety of cell lines may be used for expressing the antibody orfunctional part, including, but not limited to, mammalian cell lines. Inone embodiment, the cell lines may be human. In another embodiment,bacterial or insect cell lines may be used. In one embodiment, the celllines include Chinese hamster ovary (CHO) cells, variants of CHO cells(for example DG44), 293 cells and NSO cells. In another embodiment, celllines include VERY, BHK, Hela, COS, MDCK, 293F, 293T, 3T3, W138, BT483,Hs578T, HTB2, BT2O and T47D, CRL7O3O and HsS78Bst cells.

Recombinant expression utilizes construction of an expression vectorcontaining a polynucleotide that encodes the antibody or functionalpart. Once a polynucleotide has been obtained, a vector for theproduction of the antibody may be produced by recombinant DNA technologywell known in the art. Expression vectors may include appropriatetranscriptional and translational control signals. This may beaccomplished using in vitro recombinant DNA techniques, synthetictechniques, and in vivo genetic recombination. In one embodiment, areplicable vector comprises a nucleic acid sequence encoding an antibodyor functional part operably linked to a heterologous promoter.

A variety of host-expression vector systems may be utilized to expressantibodies or functional parts as described in U.S. Pat. No. 5,807,715.For example, mammalian cells such as Chinese hamster ovary cells (CHO),in conjunction with a vector such as the major intermediate early genepromoter element from human cytomegalovirus, are an effective expressionsystem for antibodies (Foecking et al., Gene, 45:101 (1986); and Cockettet al., Bio/Technology, 8:2 (1990)). In addition, a host cell strain maybe chosen which modulates the expression of inserted sequences, ormodifies and processes the gene product in the specific fashion desired.Such modifications (e.g., glycosylation) and processing (e.g., cleavage)of protein products may be important for the function of the protein.Different host cells have characteristic and specific mechanisms for thepost-translational processing and modification of proteins and geneproducts. Appropriate cell lines or host systems can be chosen to ensurethe correct modification and processing of the protein of the invention.To this end, eukaryotic host cells which possess the cellular machineryfor proper processing of the primary transcript, glycosylation, andphosphorylation of the gene product may be used.

In bacterial systems, a number of expression vectors may be selecteddepending upon the use intended for the antibody or functional partbeing expressed. For example, when a large quantity of such an antibodyor functional part is to be produced, for the generation ofpharmaceutical compositions comprising an antibody or functional part,vectors which direct the expression of high levels of fusion proteinproducts that are readily purified may be desirable. Such vectorsinclude, but are not limited to, the E. coli expression vector pUR278(Ruther et al., EMBO, 12:1791 (1983)), in which the coding sequence maybe ligated individually into the vector in frame with the lac Z codingregion so that a fusion protein is produced; pIN vectors (Inouye &Inouye, 1985, Nucleic Acids Res. 13:3101-3109 (1985); Van Heeke &Schuster, 1989, J. Biol. Chem., 24:5503-5509 (1989)); and the like. pGEXvectors may also be used to express foreign polypeptides as fusionproteins with glutathione-S-transferase (GST). In general, such fusionproteins are soluble and can easily be purified from lysed cells byadsorption and binding to glutathione-agarose affinity matrix followedby elution in the presence of free glutathione. The pGEX vectors aredesigned to introduce a thrombin and/or factor Xa protease cleavagesites into the expressed polypeptide so that the cloned target geneproduct can be released from the GST moiety.

In an insect system, Autographa californica nuclear polyhedrosis virus(AcNPV) is used as a vector to express foreign genes. The virus grows inSpodoptera frugiperda cells. The protein coding sequence may be clonedindividually into non-essential regions (for example, the polyhedringene) of the virus and placed under control of an AcNPV promoter (forexample, the polyhedrin promoter).

In mammalian host cells, a number of virus based expression systems maybe utilized. In cases where an adenovirus is used as an expressionvector, the coding sequence of interest may be ligated to an adenovirustranscription/translation control complex, e.g., the late promoter andtripartite leader sequence. This chimeric gene may then be inserted inthe adenovirus genome by in vitro or in vivo recombination. Insertioninto a non-essential region of the viral genome (e.g., region E1 or E3)will result in a recombinant virus that is viable and capable ofexpressing the antibody or functional part in infected hosts (e.g., see,Logan & Shenk, Proc. Natl. Acad. Sci. USA, 81:355-359 (1984)). Specificinitiation signals may also be required for efficient translation ofinserted antibody or functional part coding sequences. These signalsinclude the ATG initiation codon and adjacent sequences. Furthermore,the initiation codon should generally be in frame with the reading frameof the desired coding sequence to ensure translation of the entireinsert. These exogenous translational control signals and initiationcodons can be of a variety of origins, both natural and synthetic. Theefficiency of expression may be enhanced by the inclusion of appropriatetranscription enhancer elements, transcription terminators, etc. (see,e.g., Bittner et al., Methods in Enzymol., 153:51-544(1987)).

Stable expression can be used for long-term, high-yield production ofrecombinant proteins. For example, cell lines which stably express theprotein molecule may be generated. Host cells can be transformed with anappropriately engineered vector comprising expression control elements(e.g., promoter, enhancer, transcription terminators, polyadenylationsites, etc.), and a selectable marker gene. Following the introductionof the foreign DNA, cells may be allowed to grow for 1-2 days in anenriched media, and then are switched to a selective media. Theselectable marker in the recombinant plasmid confers resistance to theselection and allows cells that stably integrated the plasmid into theirchromosomes to grow and form foci which in turn can be cloned andexpanded into cell lines. Plasmids that encode an antibody or functionalpart can be used to introduce the gene/cDNA into any cell line suitablefor production in culture.

A number of selection systems may be used, including, but not limitedto, the herpes simplex virus thymidine kinase (Wigler et al., Cell,11:223 (1977)), hypoxanthineguanine phosphoribosyltransferase (Szybalska& Szybalski, Proc. Natl. Acad. Sci. USA, 48:202 (1992)), and adeninephosphoribosyltransferase (Lowy et al., Cell, 22:8-17 (1980)) genes canbe employed in tk-, hgprt- or aprT-cells, respectively. Also,antimetabolite resistance can be used as the basis of selection for thefollowing genes: dhfr, which confers resistance to methotrexate (Wigleret al., Natl. Acad. Sci. USA, 77:357 (1980); O'Hare et al., Proc. Natl.Acad. Sci. USA, 78:1527 (1981)); gpt, which confers resistance tomycophenolic acid (Mulligan & Berg, Proc. Natl. Acad. Sci. USA, 78:2072(1981)); neo, which confers resistance to the aminoglycoside G-418 (Wuand Wu, Biotherapy 3:87-95 (1991); Tolstoshev, Ann. Rev. Pharmacol.Toxicol. 32:573-596 (1993); Mulligan, Science 260:926-932 (1993); andMorgan and Anderson, Ann. Rev. Biochem. 62:191-217 (1993); May, TIB TECH11(5):155-2 15 (1993)); and hygro, which confers resistance tohygromycin (Santerre et al., Gene, 30:147 (1984)). Methods commonlyknown in the art of recombinant DNA technology may be routinely appliedto select the desired recombinant clone, and such methods are described,for example, in Ausubel et al. (eds.), Current Protocols in MolecularBiology, John Wiley & Sons, NY (1993); Kriegler, Gene Transfer andExpression, A Laboratory Manual, Stockton Press, NY (1990); and inChapters 12 and 13, Dracopoli et al. (eds.), Current Protocols in HumanGenetics, John Wiley & Sons, NY (1994); Colberre-Garapin et al., 1981,J. Mol. Biol., 150:1.

Once an antibody or functional part has been produced by recombinantexpression, it may be purified by any method known in the art forpurification of an immunoglobulin molecule, for example, bychromatography (e.g., ion exchange, affinity, particularly by affinityfor the specific antigens Protein A or Protein G, and sizing columnchromatography), centrifugation, differential solubility, or by anyother standard technique for the purification of proteins. Further, theproteins of the present invention or fragments thereof may be fused toheterologous polypeptide sequences described herein or otherwise knownin the art to facilitate purification.

In some embodiments, RSV-specific antibody producing cells are generatedwhich are stable for at least six months. In another embodiment, anRSV-specific antibody producing cell is stable for at least nine weeks,at least three months, or at least six months. In another embodiment,alternative methods of making antibodies and functional parts are wellknown in the art and described in at least U.S. Pat. No. 8,562,996.

Reference will now be made in detail to the present exemplaryembodiments, examples of which are illustrated in the accompanyingdrawings. Wherever possible, the same reference numbers will be usedthroughout the drawings to refer to the same or like parts. Otherembodiments will be apparent to those skilled in the art fromconsideration of the specification and practice disclosed herein. Theembodiments are further explained in the following examples. Theseexamples do not limit the scope of the claims, but merely serve toclarify certain embodiments. It is intended that the specification andexamples be considered as exemplary only, with a true scope and spiritbeing indicated by the following claims.

EXAMPLES Example 1. Preparation and Expression of Monoclonal Antibodies

The DNA fragments of 1G7 immunoglobulin variable light chain (VL) andvariable heavy chain (VH), each containing desired mutations thatimprove the antibody's potency, were inserted into a human IgG1expression vector containing the kappa light constant region and theCH1-hinge-CH2-CH3 IgG1 heavy constant region. To express 1G7 antibody,human embryonic kidney 293-F cells were transiently transfected with the1G7-containing vector using 293Fectin™ reagent (Invitrogen, Carlsbad,Calif.). Cells were grown at 37° C., 120 rpm with 5% CO₂ and 80%humidity. The culture media was fed on the second day by adding equalvolume media and harvested 10 days post transfection. The supernatantwas sterile filtered to remove cells and debris. The IgG was purifiedusing protein A column (Hi-trap protein A column, Sigma) and elutedprotein was dialyzed against PBS overnight at 4° C. The IgGconcentration was determined by protein quantitation in NanoDrop (ThermoScientific).

The 1G7-containing vector RSV mAb 1G7 pOE was deposited with theAmerican Type Culture Collection (ATCC®), 10801 University Boulevard,Manassas, Va. 20110-2209, USA under ATCC Patent Designation PTA-125140on Sep. 21, 2018. This deposit is in accordance with the Budapest Treatyon the International Recognition of the Deposit of Microorganisms forthe Purposes of Patent Procedure.

The same approach was taken to produce the other antibodies.

Example 2. In Vitro Microneutralization Assay

Microneutralization assays were performed as follows: Briefly, 2-foldserial dilutions of MAb were introduced into 384-well microtiter platesin HEp-2 cell culture medium at a volume of 15 μL/well. Subsequently, 15μL of either RSV A2 or RSV B 9320 virus diluted into HEp-2 cell culturemedium to concentration ranging from 80 to 150 pfu/well and was added toeach well including control wells containing HEp-2 cell culture mediumalone, and plates were incubated for 1.5 hours at 37° C. with 5% CO2.HEp-2 cells were added at 2.5×10⁵ cells/mL in 30 μL to each well and theplates were incubated at 37° C. with 5% CO2. After 3 days for RSV A2 or4 days for RSV B9320, medium was removed and 30 μL of ice cold 80%acetone/20% PBS was added to fix the cells.

Viral replication was measured by enzyme-linked immunosorbent assay(ELISA) using a horseradish peroxidase conjugated anti-RSV F MAbtargeting the C site of RSV F (1331H) (Beeler and van Wyke Coelingh, JVirol. 63(7):2941-2950 (1989). 1331H MAb was diluted 1:6,000 in PBS and30 μl was added to each well. Following two hours of incubation at 37°C., the plates were washed three times with PBS-T. TMB peroxidase 30 μLwas added to each well and the plates were incubated at room temperaturein the dark for 15 minutes. The reaction was stopped by the addition of15 μL of 2N H2504 to each well. Substrate turnover was measured bymonitoring absorbance at 450 nm using a microplate reader. IC50 valueswere calculated using a non-linear fit algorithm in Graphpad Prism usingthe log (inhibitor) vs. response with variable slope curve fit andrepresent the concentration of MAb required for a 50% reduction inabsorbance measured at 450 nm.

Results are provided in FIG. 4, which shows that 1G7, 1F5, 2D10, and D25each inhibited RSV A2 and RSV B9320 replication in themicroneutralization. 1G7 was the most effective, followed by 1F5, 2D10,and then D25.

Example 3. Cotton Rat RSV Model

A) Comparing the Ability of D25, J, L, and LA variants to ProtectAgainst RSV Challenge

Animals were dosed with 0.1 ml of antibody by intramuscular injection atthe various dosage levels indicated in the figure. Twenty-four hourslater, animals were anesthetized using an isoflourane chamber andinfected by intranasal instillation of 1×10⁶ pfu/animal of RSV strainA2. Four days later, animals were sacrificed by carbon dioxideasphyxiation; their lungs were surgically removed, bisected and frozenin liquid nitrogen or processed immediately. Blood samples were obtainedby cardiac puncture at the time of sacrifice.

To assess the effect of MAb administration on RSV replication in thelungs of cotton rats, RSV viral titer in cotton rat lung homogenateswere determined for each dose group. For that purpose, harvested lungswere individually homogenized in 10 parts (weight/volume) Hanks BalancedSalt Solution plus sucrose phosphate using a Fast Prep 24 tissuehomogenizer for 20 seconds with TeenALysing Matrix tubes at roomtemperature. The resulting suspensions were centrifuged at 930× g for 10min at 4° C., and the supernatants were collected and stored at −80° C.until analysis. Lung homogenate samples were diluted 1:10 and 1:100 inculture medium, and 50 μL of either undiluted lung homogenate or dilutedlung homogenate samples were added to duplicate wells of HEp-2 cellsthat had been seeded at a cell density of 2.5×10⁵ cells/well in 24-wellplates, 24 hours prior to inoculation. After 1 hour incubation at 37° C.with 5% CO₂, the inoculum was replaced with culture medium containing0.8% methylcellulose and the cells were incubated at 37° C. with 5% CO₂.Five days later the overlay was removed, and the cells were fixed andimmuno-stained with an goat anti-RSV polyclonal antibody followed by asecondary anti-goat HRP antibody. Plaques were visualized by reactionwith AEC reagent. Plaques were quantified under a microscope using a 10×objective. The limit of detection for this assay is 200 pfu/g of tissue.Samples with a viral titer below the limit of detection (<200 pfu/g)were designated at 100 pfu/g (one-half of the lower limit of detection)for purposes of the statistical analysis. Results are provided in FIG.5, demonstrating that the J, L, and LA variants are all more effectivethan D25 in protecting against RSV A challenge, but that the L and LAvariants were less effective in protecting against RSV B subtypes (withL performing better against one B strain than another). Based on thisdata, J was chosen as the starting point for further optimization.

B) Comparing the Ability of 1G7, 1F5, and D25 variants to ProtectAgainst RSV Challenge

The model discussed above in part (A) of this example was used tocompare the ability of 1G7, 1F5, and D25 to protect against RSVchallenge. Animals were dosed at 2 mg/kg, 1 mg/kg, 0.5 mg/kg, and 0.25mg/kg. Results are shown in FIG. 6. The data shows that 1G7 performedbetter than 1F5 in protecting against RSV challenge, though both wereable to reduce the virus titer to the limit of detection. Both 1G7 and1F5 performed better than D25.

C) Detailed Evaluation of 1G7 Variant

The same cotton rat model was used as described in section (A) above.Each animal received 0.1 ml of antibody, with varying concentrations ofantibody present, as reported in FIG. 7. 1G7 demonstrates adose-response relationship with RSV lung titer for both RSV A2 and RSVB9320.

D) Comparing the Ability of Variants to Neutralize RSV A2 and RSV B9320

The same cotton rat model was used as described in section (A) above.

The concentrations of human IgG in cotton rat serum samples on the dayof lung harvest were determined using an ELISA method. In this assay thehuman antibodies were captured by a goat anti-human antibody bound tomicrotiter plates. The goat anti-human IgG (H+L) antibody (0.5 μg/mL in1×PBS) was coated onto Nunc Maxisorp 384 well microtiter platesovernight at 4° C. in a 30 μL volume. Plates were washed then blockedwith 60 μL of a solution of PBS+3% heat inactivated goat serum for 1hour at room temperature. The blocking buffer was removed and sampleswere applied as follows: A two-fold serial dilution of the standardhuman antibody diluted in assay buffer was used for the standard curvewith a concentration range of 500 ng/ml to 0.488 ng/ml. Standard curveswere fitted using a 4 parameter curve fit.

Results are provided in FIG. 8, showing that the variants describedherein have lower IC50s than D25 in neutralizing both RSV A2 and RSVB9320. This also demonstrates that there was no loss of activity againstthe A2 or B9320 virus with increased activity seen with E9-2 and B12-1and only a nominal loss of activity against the B9320 virus with 1G7 GLMand E3-5.

Example 4. Epitope as Defined by Monoclonal Antibody Resistant Mutants

RSV A and RSV B virus mutants were isolated by passage three times inthe presence of 250 ng/ml of 1G7-YTE. 1G7-YTE is the 1G7 antibody withthe YTE mutation described above in section I.C above. Following thelast passage the sequence of the RSV F protein was determined. Mutationscorrespond to regions that were previously defined in the co-crystalstructure of RSV F with the parental D25 antibody. All resistant mutantscontained changes in the region of RSV F protein in the F1 regionbetween amino acids 200-213. Secondary mutations at position 294 werenot shown to enhance resistance and were no more resistant than thosewith a single mutation in the region 200-213. Secondary mutations in theF2 region of the N2085 mutation background resulted in enhancedresistance. Results are provided in FIG. 9.

The 1G7-YTE antibody is encoded by the RSV mAb 1G7 pOE YTE vector,deposited with the American Type Culture Collection (ATCC®), 10801University Boulevard, Manassas, Va. 20110-2209, USA under ATCC PatentDesignation PTA-125141 on Sep. 21, 2018. This deposit is in accordancewith the Budapest Treaty on the International Recognition of the Depositof Microorganisms for the Purposes of Patent Procedure.

Example 5. Neutralization Against Clinical Isolates of RSV

A neutralization assay was performed by pre-incubation of the expandedclinical isolate viruses with a dilution series of the antibodies priorto infection of HEp2 cells. Infection of cells was measured as afunction of F protein expression on the surface of the cells. IC50values were calculated by non-linear fitting of neutralization curves.Viral replication was measured as in Example 2 (In VitroMicroneutralization Assay).

Results are provided in FIG. 10. The IC50 for 1G7 and 1F5 are both lowerthan D25 for neutralizing either A isolates or B isolates of RSV in HEp2cells.

INCORPORATION BY REFERENCE

All references cited herein, including patents, patent applications,papers, text books, and the like, and the references cited therein, tothe extent that they are not already, are hereby incorporated herein byreference in their entirety for all purposes.

EQUIVALENTS

The foregoing written specification is considered to be sufficient toenable one skilled in the art to practice the embodiments. The foregoingdescription and Examples detail certain embodiments and describes thebest mode contemplated by the inventors. It will be appreciated,however, that no matter how detailed the foregoing may appear in text,the embodiments may be practiced in many ways and the claims include anyequivalents thereof.

What is claimed is:
 1. An antibody or a functional part thereof capableof specifically binding the Respiratory Syncytial Virus (RSV) F protein,the antibody or functional part thereof comprising the heavy and lightchain variable region CDRs 1-3 encoded by the 1G7-containing vectordeposited at the ATCC under Patent Designation PTA-125140.
 2. Theantibody or a functional part thereof of claim 1, comprising a leucine(L) at amino acid position 28, a glutamic acid (E) at amino acidposition 30, a valine (V) at amino acid position 37, a glycine (G) atamino acid position 61, a methionine (M) at amino acid position 81, aglutamic acid (E) at amino acid position 82, and a serine (S) at aminoacid position 84 of the heavy chain variable region, wherein thenumbering corresponds to the EU index in Kabat.
 3. The antibody or afunctional part thereof of claim 1, wherein the antibody or a functionalpart thereof is fully human, humanized, or chimeric.
 4. The functionalpart thereof of claim 1, wherein the functional part thereof is a singlechain antibody, a single chain variable fragment (scFv), a Fab fragment,or a F(ab′)₂ fragment.
 5. The antibody or a functional part thereof ofclaim 1, comprising a human IgG1 isotype.
 6. The antibody or afunctional part thereof of claim 1, wherein the antibody or a functionalpart thereof comprises a human IgG isotype and comprises an Fc regioncomprising tyrosine (Y) at amino acid position 252, threonine (T) atamino acid position 254, and glutamic acid (E) at amino acid position256, wherein the numbering corresponds to the EU index in Kabat.
 7. Theantibody or a functional part thereof of claim 6, wherein the IgGisotype is IgG1.
 8. An antibody or a functional part thereof capable ofspecifically binding the Respiratory Syncytial Virus (RSV) F protein,the antibody or a functional part thereof comprising the heavy and lightchain variable regions (VH and VL) encoded by the 1G7-containing vectordeposited at the ATCC under Patent Designation PTA-125140.
 9. Anantibody or a functional part thereof which is capable of specificallybinding the Respiratory Syncytial Virus (RSV) F protein and is a fullyhuman or chimeric form of an antibody comprising the heavy and lightchain variable regions (VH and VL) encoded by the 1G7-containing vectordeposited at the ATCC under Patent Designation PTA-125140.
 10. Thefunctional part thereof of claim 8, wherein the functional part thereofis a single chain antibody, a single chain variable fragment (scFv), aFab fragment, or a F(ab′)₂ fragment.
 11. The antibody or a functionalpart thereof of claim 8, wherein the antibody or a functional partthereof comprises a human IgG isotype and comprises an Fc regioncomprising tyrosine (Y) at amino acid position 252, threonine (T) atamino acid position 254, and glutamic acid (E) at amino acid position256, wherein the numbering corresponds to the EU index in Kabat.
 12. Theantibody or a functional part thereof of claim 11, wherein the IgGisotype is IgG1.
 13. An antibody or a functional part thereof encoded bythe 1G7-containing vector deposited at the ATCC under Patent DesignationPTA-125140 capable of specifically binding the Respiratory SyncytialVirus (RSV) F protein.
 14. The functional part thereof of claim 13,wherein the functional part thereof is a single chain antibody, a singlechain variable fragment (scFv), a Fab fragment, or a F(ab′)₂ fragment.15. An antibody encoded by the 1G7-containing vector deposited at theATCC under Patent Designation PTA-125140 capable of specifically bindingthe Respiratory Syncytial Virus (RSV) F protein.
 16. An antibody encodedby the RSV mAb 1G7 pOE YTE vector deposited at the ATCC under PatentDesignation PTA-125141 capable of specifically binding the RespiratorySyncytial Virus (RSV) F protein.